The unique ultrastructure of secretory membranes in gastric parietal cells depends upon the presence of H⁺, K⁺-ATPase

Abstract.

Ion transporters play a central role in gastric acid secretion. To determine whether some of these transporters are necessary for the normal ultrastructure of secretory membranes in gastric parietal cells, mice lacking transporters for H⁺, K⁺, Cl^–, and Na⁺ were examined for alterations in volume density (Vd) of basolateral, apical, tubulovesicular and canalicular membranes, microvillar dimensions, membrane flexibility, and ultrastructure. In mice lacking Na⁺/H⁺ exchanger 1 (NHE1) or the Na⁺-K⁺-2Cl^– cotransporter (NKCC1), the ultrastructure and Vd of secretory membranes and the secretory canalicular to tubulovesicular membrane ratio (SC/TV), a morphological correlate of secretory activity, were similar to those of wild-type mice. In mice lacking Na⁺/H⁺ exchanger 2 (NHE2) or gastric H⁺, K⁺-ATPase α- or β-subunits, the SC/TV ratio and Vd of secretory membranes were decreased, though canaliculi were often dilated. In H⁺, K⁺-ATPase-deficient parietal cells, canalicular folds were decreased, normally abundant tubulovesicles were replaced with a few rigid round vesicles, and microvilli were sparse, stiff and short, in contrast to the long and flexible microvilli in wild-type cells. In addition, microvilli of the H⁺, K⁺-ATPase-deficient parietal cells had centrally bundled F-actin filaments, unlike the microvilli of wild-type cells, in which actin filaments were peripherally positioned concentric to the plasmalemma. Data showed that the absence of H⁺, K⁺-ATPase produced fundamental changes in parietal cell membrane ultrastructure, suggesting that the pump provides an essential link between the membranes and F-actin, critical to the gross architecture and suppleness of the secretory membranes.